Pendred syndrome and DFNB4‐mutation screening of <i>SLC26A4</i> by denaturing high‐performance liquid chromatography and the identification of eleven novel mutations

Prasad, Sai; Kölln, Karen A.; Cucci, Robert A.; Trembath, Richard C.; Camp, Guy Van; Smith, Richard J.H.

doi:10.1002/ajmg.a.20272

Cited by 63 publications

(48 citation statements)

References 20 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to two common mutations, the novel Q421P mutation was identified in this study. The Q421R mutation at the same position was reported in the study of Prasad et al (2004) [44] and the functional studies of the similar location such as T416P mutation suggest that the change of amino acid at this position occurred the cause of disease [45,46]. We demonstrated severe to profound hearing impairment in 7 patients with inner ear malformations, consistent with the results of previous studies [30,42].…”

Section: Discussionsupporting

confidence: 90%

Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients

Lee

Choi

Bae

et al. 2008

International Journal of Pediatric Otorhinolaryngology

View full text Add to dashboard Cite

Objective-Mutations in the GJB2, GJB6 and SLC26A4 genes are a frequent cause of hearing loss in a number of populations. However, little is known about the genetic causes of hearing loss in the Korean population.Methods-We sequenced the GJB2 and GJB6 genes to examine the role of mutations in these genes in twenty-two hearing loss patients. We also sequenced the SLC26A4 gene in seven patients with inner ear malformations, including enlarged vestibular aqueduct (EVA) revealed by computer tomography.Results-Coding sequence mutations in GJB2 were identified in 13.6% of the patients screened. Two different mutations, 235delC and T86R were found in three unrelated patients. The 235delC was the most prevalent mutation with an allele frequency of 6.9% in our patient group. No mutations, including 342 kb deletion, were found in GJB6 gene. Three different variants of SLC26A4 were identified in the EVA patients, including one novel mutation. Four EVA patients carried two mutant alleles of SLC26A4, and at least one allele in all patients was the H723R mutation, which accounted for 75% of all mutant alleles.Conclusions-Our results suggest that GJB2 and SLC26A4 mutations together make up a major cause of congenital hearing loss in the Korean population. Further studies may be able to identify other common variants that account for a significant fraction of hearing loss in the Korean population.

show abstract

Section: Discussionsupporting

confidence: 90%

Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients

Lee

Choi

Bae

et al. 2008

International Journal of Pediatric Otorhinolaryngology

View full text Add to dashboard Cite

show abstract

“…The p.E29Q allele has been reported in two French patients 9,13 and in other three cases of unknown ethnic origin 11,20,24 and except in one patient, it is accompanied by a second mutation. The p.D724G mutation has only been described in one patient of unknown ethnic origin who also carried a second mutation, 20 as well as in our previously published Spanish family. 23 We did not find the p.D724G variant in the first screening of 70 healthy controls, but it was found twice when we augmented the size of the control population to 214 individuals.…”

Section: Discussionmentioning

confidence: 86%

A mutational analysis of the SLC26A4 gene in Spanish hearing-impaired families provides new insights into the genetic causes of Pendred syndrome and DFNB4 hearing loss.

et al. 2008

View full text Add to dashboard Cite

Pendred syndrome (PS) and DFNB4, a non-syndromic sensorineural hearing loss with enlargement of the vestibular aqueduct (EVA), are caused by mutations in the SLC26A4 gene. Both disorders are recessive, and yet only one mutated SLC26A4 allele, or no mutations, are identified in many cases. Here we present the genetic characterization of 105 Spanish patients from 47 families with PS or non-syndromic EVA and 20 families with recessive non-syndromic hearing loss, which segregated with the DFNB4 locus. In this cohort, two causative SLC26A4 mutations could be characterized in 18 families (27%), whereas a single mutated allele was found in a patient with unilateral hearing loss and EVA in the same ear. In all, 24 different causative mutations were identified, including eight novel mutations. The novel p.Q514K variant was the most prevalent mutation in SLC26A4, accounting for 17% (6/36) of the mutated alleles identified in this study, deriving from a founder effect. We also characterized a novel multiexon 14 kb deletion spanning from intron 3 to intron 6 (g.8091T_22145Cdel). This study also revealed the first case of a de novo recessive mutation p.Q413P causing PS that arose in the proband's paternal allele, the maternal one carrying the p.L445W. The relevance of our results for genetic diagnosis of PS and non-syndromic EVA hearing loss is discussed.

show abstract

“…We performed direct sequencing of all 21 exons of the SLC26A4 gene and its exon/intron boundaries using previously published primers (Prasad et al, 2004). In brief: After PCR, fragments were purified with AMPure set (Beckman Coulter, Beverly, MA, USA) and sequenced with the Big Dye Terminator 3.1 kit (Applied Biosystems, Foster City, CA, USA).…”

Section: Molecular Genetic Analysismentioning

confidence: 99%

Spectrum and Frequency of SLC26A4 Mutations Among Czech Patients with Early Hearing Loss with and without Enlarged Vestibular Aqueduct (EVA)

Pourová

Janoušek²,

Jurovčík³

et al. 2010

Annals of Human Genetics

View full text Add to dashboard Cite

SummaryMutations in SLC26A4 cause Pendred syndrome (PS) -hearing loss with goitre -or DFNB4 -non-syndromic hearing loss (NSHL) with inner ear abnormalities such as Enlarged Vestibular Aqueduct (EVA) or Mondini Dysplasia (MD). We tested 303 unrelated Czech patients with early hearing loss (298 with NSHL and 5 with PS), all GJB2-negative, for SLC26A4 mutations and evaluated their clinical and radiological phenotype. Among 115 available HRCT/MRI scans we detected three MD (2.6%), three Mondini-like affections (2.6%), 16 EVA (13 bilateral -19.2% and 15.6% respectively) and 61 EVA/MD-negative scans (73.4%). We found mutation(s) in 26 patients (8.6%) and biallelic mutations in eight patients (2.7%) out of 303 tested. In 18 of 26 (69%) patients, no second mutation could be detected even using MLPA. The spectrum of SLC26A4 mutations in Czech patients is broad without any prevalent mutation. We detected 21 different mutations (four novel). The most frequent mutations were p.Val138Phe and p.Leu445Trp (18% and 8.9% of pathogenic alleles respectively). Among 13 patients with bilateral EVA, six patients (50%) carry biallelic mutations. In EVA -negative patients no biallelic mutations were found but 4.9% had monoallelic mutations. SLC26A4 mutations are present mostly in patients with EVA/MD and/or progressive HL and those with affected siblings.

show abstract

Pendred syndrome and DFNB4‐mutation screening of SLC26A4 by denaturing high‐performance liquid chromatography and the identification of eleven novel mutations

Cited by 63 publications

References 20 publications

Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients

Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients

A mutational analysis of the SLC26A4 gene in Spanish hearing-impaired families provides new insights into the genetic causes of Pendred syndrome and DFNB4 hearing loss.

Spectrum and Frequency of SLC26A4 Mutations Among Czech Patients with Early Hearing Loss with and without Enlarged Vestibular Aqueduct (EVA)

Contact Info

Product

Resources

About